New Simple Polymeric Supports with Hydrazone Linkers for Solid-Phase Synthesis of Ketones and Primary Amines

Abstract

The preparation of new solid supports with hydrazine anchoring groups and their application to solid-phase synthesis of ketones and primary amines are described. The supports were used for immobilization of ketones, 4-tert-butylcyclohexanone, pentan-3-one, acetone, N-methylpiperidone, N-benzylpiperidone, and tropinone in the form of their hydrazones. The polymer-supported hydrazones were subjected to deprotonation/alkylation procedure (LDA/RX) once or twice. The resulting alkylated products were cleaved off the solid support on treatment with trifluoroacetic acid in tetrahydrofuran providing a-alkylated or a,a¢-bisalkylated ketones or were subjected to reductive cleavage with borane in tetrahydrofuran to give b-alkylated or b,b¢-bisalkylated primary amines.

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

“…296 The polymers with N,N-dialkylhydrazine functional groups that could be used for binding carbonyl compounds as hydrazones are not available commercially, and therefore, synthesis of polymer-supported hydrazines is a precondition. The supported N,N-dialkylhydrazines have been prepared on Merrifield-type polymers by typical reduction of previously produced N-nitrosoamines, [299][300][301][302][303][304] anchoring protected N,Ndialkylhydrazines, 62,[305][306][307] or the direct functionalization of the polymer with N-alkylhydrazine. 46 The last method is the simplest but may be limited by poor regioselectivity of monalkyl hydrazine alkylation.…”

Biodegradable Chitosan‐Derived Thioureas as Recoverable Supported Organocatalysts – Application to the Stereoselective Aza‐Henry Reaction

“…N ‐Boc 3‐aminopropanal ( 1 , Boc = tert ‐butoxycarbonyl), and Fmoc 5‐aminopentanal ( 2 , Fmoc = 9‐fluorenylmethoxycarbonyl) were obtained in two steps from 3‐aminopropanol and 5‐aminopentanol, respectively. 6‐( N ‐methylamino)hexanol ( 3 ) was prepared by the total lithium aluminum hydride (LAH) reduction of Boc‐6‐amino hexanoic acid. The treatment of 3 with Boc‐ l ‐valine or Boc‐ l ‐phenylalanine yielded hydroxyamides 4 and 5 , respectively, in excellent yields.…”

“…Chitosan (molecular weight: 600,000–800,000 Da) was purchased from ACROS Organics. Protected amino aldehydes 1 and 2 , amino alcohol 3 , isothiocyanates 10 [22c] and 11 ,[22c] and Boc‐protected imines 24a – 24f [22a] were prepared according to literature procedures. Racemic reference samples were prepared by using 1,4‐diazabicyclo[2.2.2]octane (DABCO, 5 mol‐%) according to the procedure described below.…”

N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis

“…[86][87][88][89][90][91][92][93][94][95][96][97] Other very similar linkers based on reductive amination include the formylindolylmethyltriazole (FIMT) linker, 98 the 2-methoxy-4-alkoxybenzyl linker, 99 the acid-sensitive methoxybenzaldehyde (AMEBA) linker, 100 and the pbenzyloxybenzylamine (BOBA) linker. 101 Recently, a linker strategy employing a hydrazone moiety was introduced by Lazny et al 102,103 Alkyl hydrazine linker 19 was treated with either an aldehyde or a ketone to give the resin-bound hydrazone 20 (Scheme 5). Successive deprotonation/lithiation with excess lithium diisopropylamide (LDA) and alkylation with alkyl halides were performed once or twice to give monoor di-b-alkylated resin-bound hydrazones (the example shown, 21, is dialkylated).…”

“…103 Scheme 5 Synthesis of b-substituted primary amines from ketones using the hydrazone linker strategy. 102,103 A related linker developed by Enders and co-workers was employed in the preparation of a-alkylated primary amines. 104 Bräse and co-workers developed a system in which the stable diazonium ion linker 23 was applied to the immobilization of primary amines to give 24.…”